Relation of transdermal nitroglycerin efficacy with dosage in different subsets of patients

Abstract

Two single-blind placebo-controlled studies were consecutively performed with nitroglycerin (NTG) (5 and 10 mg/24 hours) patches in 24 patients with stable angina pectoris. The relation of NTG patch efficacy with dosage and different subsets of patients during acute and chronic patch therapy was analyzed. NTG patch effects were assessed by multistage treadmill exercise test at 5, 16, 20 and 24 hours after patch application, during single patch administration and after 3 months of continuous therapy, with washout phases as well as with 1-and 7-day placebo patch periods. The analysis of differences between NTG and placebo patch demonstrated significant improvement of exercise capacity in the total group of 24 patients. A taxonomy analysis revealed 2 different subsets in the sample of 24 patients, having similar exercise ST depression but different exercise walking times in the washout period. Group I (15 patients), with an initial 68% of maximal predicted time, showed moderate increases in magnitude of exercise efficacy during the acute and chronic period, with low decrease of effects over 24 hours. Efficacy was greater during the chronic phase, with evident dose relation of all changes. Group II (9 patients), with 40% of maximal predicted time, demonstrated an increased efficacy during acute and chronic therapy, with a steep decrease of all values over 24 hours and significant improvement of exercise tolerance during chronic therapy; these changes were not mainly dose-related. These differences in the magnitude and in the pattern of exercise efficacy over 24 hours, during acute and chronic NTG patch therapy, could probably be attributed to different nitrate mechanisms of action, depending on the pathophysiologic characteristics of stable angina pectoris in 2 subsets of patients. The controversies about NTG patch efficacy have been discussed with regard to relation between multiple modes of nitrate action and the subsets of patients with different prevailing mechanisms of stable angina pectoris.